Several techniques for the preparation of products in the form of micro granules have been developed. In them, the mix of active substances and excipients can be subjected to a procedure of mixing, kneading, spheronization, coating, etc. So, there is equipment for palletization, coating dishes, fluid bed machines, extrusion machines, centrifuges, and others.
In the patent documents EP247983 y EP244380, the active substance is kneaded by wet process with a mixture of excipients that allows to create and alkaline microenvironment. The mixture is then extruded and spheronized. The spheronized microgranules are coated with one or more intermediated layers of water soluble, alkaline, buffering, polymeric excipients, later an outer gastro-resistant layer is applied.
Patent ES2052697 shows an example of coating with dust distributed with the use of roto-granules. Spherical granules are described, that have a nucleus clad with dust that contains a benzimidazolium anti-ulceric compound and hidroxypropyl cellulose of low grade of substitution. A procedure to produce the aforementioned spherical granules is also described, that is characterized because the nuclei are wetted by nebulization with an agglutinant solution and sprinkled with a dust containing the active substance. The pharmaceutical preparations and food supplements, prepared with these techniques, present the difficulty of liberation of the active substance.
In the publication WO1999006032 a pharmaceutical preparation is described, that comprehends an inert nucleus, an active layer that is water soluble or of rapid disintegration in water that was obtained from an aqueous or hydroalcoholic solution. A procedure is also described, which is carried out through the coating of the inert nuclei through the nebulization of the aqueous or hydroalcoholic suspension, the drying of the active layer formed during the nebulization of the previous step, the coating of the charged nuclei through an external gastro-resistant layer.
In the publication U.S. Pat. No. 5,585,050 micro capsules that contain at least one active substance are described, which is constituted by an internal, hydrophilic, essentially non-aqueous nucleus, formed from the dissolution of, at least, one active substance that is water soluble and amphoteric in, at least, one non-aqueous hydrophilic solvent, and from a wall that encompasses the internal nucleus based on, at least, one polymer or copolymer. These micro capsules have application in systems of instantaneous release of the active ingredient, such as hygiene items, gloves and surgery materials.
The document ES2080703 describes stabilization methods of drug substances incorporated to gum tablets, which consist of micro-encapsulation of the active drug substance or substances, through a product of micro-encapsulation, whose main component is egg albumin and in which glycyrrhizinate ammonium, aspartame, iso-octane, deionized water and span. The active substances are dissolved separately, along with albumin, glycyrrhizinate ammonium and aspartame in deionized water, with the later addition of iso-octane and span, and stirring to form an emulsion that is heated up to 60° C. and is applied to a sieve of square apertures; leaving it in conditions to be incorporated, by conventional methods, to the gum mass.
The document ES2209973 refers to a combination that comprehends glucosamine and hyper-immunized egg, where the combination can be concomitant or a mixture. The methods for its mixing are conventional, not alluding the use of an ultrasonic nebulizing equipment for the mixing.
According to the results of the study of the art, several companies and research centers dedicated to the production of isolated proteins from egg fractions, are interested in creasing and diversify the use of some components, such as ovalbumin and ovotransferin. Particularly, the industries dedicated to the production of lysozyme, used as an antimicrobial agent, that obtain as byproducts other nitrogenated low cost fractions, generally destined for animal feeding or for their use as emulsifier and gelifier in diverse foods.
On the other hand, many properties have been discovered on flavonoids (flavones, flavonols, flavonones, flavonol, antoganins and isoflavones), such as, antioxidants, anti-allergenic, anti-inflammatory, antibiotic and anti-viral. Scientific studies have indicated that those actions are performed through the mechanism of action modulation of enzymatic activity, inhibition of malignant-cell proliferation, inhibition of the enzyme lipoxygenase that transforms arachidonic acid on leukotrienes, which mediate allergenic and inflammatory processes, as well as inhibition of the enzyme ATPase, dependent on calcium and the AMP phosphodiesterase, which act in conjunction for the liberation of histamine, with which the allergenic reaction takes place.
The flavonoid's potential protector has been shown over two main mechanisms, which with oxidative stress and inflammation, through the inhibition of interleukin, tumor necrosis factor alpha and inducible oxide synthase.
Recent studies indicate that the ingestion of flavonoids improves cognitive processes, particularly learning and memory, associated to the activation of molecular signaling cascades that promote synaptic plasticity and neurogenesis in regions of cognitive interest, like hippocampus and brain cortex.